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Biomedical Materials (Bristol, England) Jun 2021Elimination of tumor cells is still a therapeutic challenge for breast cancer (BC) in men and women. Mammospheres serve as valuabletools for evaluating tumor behavior...
Elimination of tumor cells is still a therapeutic challenge for breast cancer (BC) in men and women. Mammospheres serve as valuabletools for evaluating tumor behavior and sensitivity to anticancer treatments. Graphene nanosheets with unique physicochemical properties have been considered as potential biomedical approaches for drug delivery, bioimaging, and therapy. Graphene oxide (GO) and graphene quantum dots (GQDs) are suitable nanocarriers for hydrophobic and low bioaccessible anti-tumor materials like curcumin. Despite extensive studies on the potential application of graphene nanosheets in medicine, our knowledge of how different cells function and respond to these nanoparticles remains limited. Here, we evaluated cell death in mammospheres from MCF-7 and primary tumor cells in response to curcumin loaded on graphene nanosheets. Mammospheres were exposed to graphene oxide-curcumin (GO-Cur) and graphene quantum dots-curcumin (GQDs-Cur), and the incidence of cell death was evaluated by Hoechst 33342/propidium iodide double staining and flow cytometry. Besides, the expression of miR-21, miR-29a, Bax, and Bcl-2 genes were assessed using RT-qPCR. We observed, GO, and GQDs had no cytotoxic effect on Kerman male breast cancer/71 (KMBC/71) and MCF-7 tumor cells, while curcumin induced death in more than 50% of tumor cells. GO-Cur and GQDs-Cur synergistically enhanced anti-tumor activity of curcumin. Moreover, GQDs-Cur induced cell death in almost all cells of KMBC/71 mammospheres (99%;< 0.0001). In contrast, GO-Cur induced cell death in only 21% of MCF-7 mammosphere cells (< 0.0001). Also, the expression pattern of miR-21, miR-29a, and Bax/Bcl-2 ratio in KMBC/71 and MCF-7 mammospheres was different in response to GO-Cur and GQDs-Cur. Although KMBC/71 and MCF-7 tumor cells had similar clinical features and displayed similar responses to curcumin, more investigations are needed to clarify the detailed molecular mechanisms underlying observed differences in response to GO-Cur and GQDs-Cur.
Topics: Apoptosis; Breast Neoplasms; Cell Survival; Curcumin; Female; Graphite; Humans; MCF-7 Cells; Male; Quantum Dots; Spheroids, Cellular; Tumor Cells, Cultured
PubMed: 34020433
DOI: 10.1088/1748-605X/ac0400 -
Journal of the American Chemical Society Jan 2020Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer...
Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing elements remains a challenging open problem. Here we report the development of biomimetic cancer cell coated zeolitic imidazolate frameworks (ZIFs) for targeted and cell-specific delivery of this genome editing machinery. Coating ZIF-8 that is encapsulating CRISPR/Cas9 (CC-ZIF) with a cancer cell membrane resulted in the uniformly covered C-ZIF. Incubation of C-ZIF with MCF-7, HeLa, HDFn, and aTC cell lines showed the highest uptake by MCF-7 cells and negligible uptake by the healthy cells (i.e., HDFn and aTC). As to genome editing, a 3-fold repression in the EGFP expression was observed when MCF-7 were transfected with C-ZIF compared to 1-fold repression in the EGFP expression when MCF-7 were transfected with C-ZIF. In vivo testing confirmed the selectivity of C-ZIF to accumulate in MCF-7 tumor cells. This supports the ability of this biomimetic approach to match the needs of cell-specific targeting, which is unquestionably the most critical step in the future translation of genome editing technologies.
Topics: Animals; Biomimetics; CRISPR-Cas Systems; HeLa Cells; Heterografts; Humans; MCF-7 Cells; Metal-Organic Frameworks; Mice
PubMed: 31931564
DOI: 10.1021/jacs.9b11638 -
Analytical and Bioanalytical Chemistry Apr 2020Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative...
Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search. With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs. The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions. With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively. Graphical abstract.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Female; Glycopeptides; Glycosylation; Humans; MCF-7 Cells; Membrane Glycoproteins; Neoplastic Stem Cells; Proteomics; Tandem Mass Spectrometry
PubMed: 32030495
DOI: 10.1007/s00216-020-02453-7 -
International Journal of Molecular... Jan 2022Fluorescent carbon dots (CDs) are potential tools for the labeling of cells with many advantages such as photostability, multicolor emission, small size, rapid uptake,...
Intracellular Trafficking of Cationic Carbon Dots in Cancer Cell Lines MCF-7 and HeLa-Time Lapse Microscopy, Concentration-Dependent Uptake, Viability, DNA Damage, and Cell Cycle Profile.
Fluorescent carbon dots (CDs) are potential tools for the labeling of cells with many advantages such as photostability, multicolor emission, small size, rapid uptake, biocompatibility, and easy preparation. Affinity towards organelles can be influenced by the surface properties of CDs which affect the interaction with the cell and cytoplasmic distribution. Organelle targeting by carbon dots is promising for anticancer treatment; thus, intracellular trafficking and cytotoxicity of cationic CDs was investigated. Based on our previous study, we used quaternized carbon dots (QCDs) for treatment and monitoring the behavior of two human cancer cell MCF-7 and HeLa lines. We found similarities between human cancer cells and mouse fibroblasts in the case of QCDs uptake. Time lapse microscopy of QCDs-labeled MCF-7 cells showed that cells are dying during the first two hours, faster at lower doses than at higher ones. QCDs at a concentration of 100 µg/mL entered into the nucleus before cellular death; however, at a dose of 200 µg/mL, blebbing of the cellular membrane occurred, with a subsequent penetration of QCDs into the nuclear area. In the case of HeLa cells, the dose-depended effect did not happen; however, the labeled cells were also dying in mitosis and genotoxicity occurred nearly at all doses. Moreover, contrasted intracellular compartments, probably mitochondria, were obvious after 24 h incubation with 100 µg/mL of QCDs. The levels of reactive oxygen species (ROS) slightly increased after 24 h, depending on the concentration, thus the genotoxicity was likely evoked by the nanomaterial. A decrease in viability did not reach IC 50 as the DNA damage was probably partly repaired in the prolonged G0/G1 phase of the cell cycle. Thus, the defects in the G2/M phase may have allowed a damaged cell to enter mitosis and undergo apoptosis. The anticancer effect in both cell lines was manifested mainly through genotoxicity.
Topics: Animals; Biological Transport; Carbon; Cell Line; Cell Proliferation; Cell Survival; DNA Damage; Fibroblasts; G2 Phase Cell Cycle Checkpoints; HeLa Cells; Humans; MCF-7 Cells; Mice; Neoplasms; Optical Imaging; Quantum Dots; Reactive Oxygen Species; Time-Lapse Imaging
PubMed: 35162996
DOI: 10.3390/ijms23031077 -
Cancer Gene Therapy Jul 2022Aberrant Notch signaling is implicated in breast cancer progression, and recent studies have demonstrated links between the Notch pathway components Notch1 and Notch1...
Aberrant Notch signaling is implicated in breast cancer progression, and recent studies have demonstrated links between the Notch pathway components Notch1 and Notch1 intracellular domain (N1ICD) with poor clinical outcomes. Growing evidence suggests that Notch signaling can be regulated by small extracellular vesicles (SEVs). Here, we used breast cancer cell models to examine whether SEVs are involved in functional Notch signaling. We found that Notch components are packaged into MDA-MB-231- and MCF-7-derived SEVs, although higher levels of N1ICD were detected in SEVs from the more aggressive MDA-MB-231 cell line than from poorly invasive MCF-7 cells. SEV-Notch components were functional, as SEVs cargo from MDA-MB-231 cells induced the expression of Notch target genes in MCF-7 cells and triggered a more invasive and proliferative phenotype concomitant with the acquisition of mesenchymal features. Neutralization of the N1ICD cargo in MDA-MB-231-derived SEVs significantly reduced their potential to enhance the aggressiveness of MCF-7 cells in vitro and in a xenograft model. Overall, our results indicate that a SEV-mediated non-classical pathway of Notch signal transduction in breast cancer models bypasses the need for classical ligand-receptor interactions, which may have important implications in cancer.
Topics: Breast Neoplasms; Cell Line, Tumor; Extracellular Vesicles; Female; Humans; MCF-7 Cells; Receptor, Notch1; Signal Transduction
PubMed: 35022518
DOI: 10.1038/s41417-021-00411-8 -
PloS One 2022Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains...
Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin.
Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR). The effect of supernatants on the cytotoxicity of cisplatin (cisPt) towards the cells was also examined. Supernatants, especially from a day 1 PRBCs, both LR and NLR, reduced the viability and inhibited proliferation of tumor cells (LoVo, MCF7), accompanying by the excessive ROS production, but these were not the case in MCF-10A. Moreover, supernatants had no effect on the cytotoxicity of cisPt against LoVo and MCF7 cells, while caused increased drug resistance in MCF-10A cells. The findings suggest the acellular fraction of PRBCs does not exhibit any pro-proliferative activity in the cancer cell lines studied. However, these are pioneering issues and require further research.
Topics: Adenocarcinoma; Breast Neoplasms; Cisplatin; Colon; Epithelial Cells; Erythrocytes; Female; Humans; MCF-7 Cells; Reactive Oxygen Species
PubMed: 35802725
DOI: 10.1371/journal.pone.0271193 -
Chemical Communications (Cambridge,... Feb 2023In this work, we constructed a novel membrane fusion strategy for extracellular vesicles (EVs) and red blood cell membrane vesicles (RVs). A nanoscale space is formed,...
In this work, we constructed a novel membrane fusion strategy for extracellular vesicles (EVs) and red blood cell membrane vesicles (RVs). A nanoscale space is formed, which can improve the efficiency of the probe reaction with miRNA-21, which allows the fluorescence detection of miRNA-21 in EVs.
Topics: Humans; MCF-7 Cells; Extracellular Vesicles; Erythrocyte Membrane; MicroRNAs
PubMed: 36723001
DOI: 10.1039/d2cc05954a -
Cell Biochemistry and Function 2008The influence of 2-methoxyestradiol (2ME) was investigated on cell growth, morphology and spindle formation in a tumorigenic (MCF-7) and non-tumorigenic (MCF-12A)... (Comparative Study)
Comparative Study
The influence of 2-methoxyestradiol (2ME) was investigated on cell growth, morphology and spindle formation in a tumorigenic (MCF-7) and non-tumorigenic (MCF-12A) epithelial breast cell line. Inhibition of cell growth was more pronounced in the MCF-7 cells compared to the MCF-12A cells following 2ME treatment. Dose-dependent studies (10(-5)-10(-9) M) revealed that 10(-6) M 2ME inhibited cell growth by 44% in MCF-12A cells and by 84% in MCF-7 cells (p-value < 0.05). 2ME-treated MCF-7 cells showed abnormal metaphase cells, membrane blebbing, apoptotic cells and disrupted spindle formation. These observations were either absent or less prominent in MCF-12A cells. 2ME had no effect on the length of the cell cycle between S-phase and the time a mitotic peak was reached in either cell line but MCF-7 cells were blocked in mitosis with no statistically significant alterations in the phosphorylation status of Cdc25C. Nevertheless, Cdc2 activity was significantly increased in MCF-7 cells compared to MCF-12A cells (p-value < 0.05). The results indicate that 2ME disrupts mitotic spindle formation and enhances Cdc2 kinase activity, leading to persistence of the spindle checkpoint and thus prolonged metaphase arrest that may result in the induction of apoptosis. The tumorigenic MCF-7 cells were especially sensitive to 2ME treatment compared to the normal MCF-12A cells. Therefore, differential mechanism(s) of growth inhibition are evident between the normal and tumorigenic cells.
Topics: 2-Methoxyestradiol; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Proliferation; Estradiol; Female; Growth Inhibitors; Humans; Mitosis; Spindle Apparatus
PubMed: 18508385
DOI: 10.1002/cbf.1489 -
Journal of Zhejiang University....In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell...
In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell lines (MCF-7, A549, Hela, PC3, and HepG2 cells) were determined and the antitumor mechanisms of GTPs in MCF-7 cells were analyzed. The results showed that GTPs exhibited a broad spectrum of inhibition against the detected cancer cell lines, particularly the MCF-7 cells. Studies on the mechanisms revealed that the main modes of cell death induced by GTPs were cell cycle arrest and mitochondrial-mediated apoptosis. Flow cytometric analysis showed that GTPs mediated cell cycle arrest at both G1/M and G2/M transitions. GTP dose dependently led to apoptosis of MCF-7 cells via the mitochondrial pathways, as evidenced by induction of chromatin condensation, reduction of mitochondrial membrane potential (ΔΨ), improvement in the generation of reactive oxygen species (ROS), induction of DNA fragmentation, and activations of caspase-3 and caspase-9 in the present paper.
Topics: A549 Cells; Apoptosis; Caspase 3; Caspase 9; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Chromatin; DNA Fragmentation; Flow Cytometry; Guanosine Triphosphate; HeLa Cells; Hep G2 Cells; Humans; MCF-7 Cells; Membrane Potential, Mitochondrial; Mitochondria; Polyphenols; Reactive Oxygen Species; Tea
PubMed: 28124838
DOI: 10.1631/jzus.B1600022 -
Nutrition and Cancer 2022This systematic review was performed with a focus on the effects of quercetin (QT) on the human breast cancer cell lines MCF-7 and MDA-MB-231. PubMed, Scopus, Science...
This systematic review was performed with a focus on the effects of quercetin (QT) on the human breast cancer cell lines MCF-7 and MDA-MB-231. PubMed, Scopus, Science Direct, and Google Scholar databases were searched up to May 2020 using relevant keywords. All articles written in English evaluating the effects of QT on the human breast cancer cell lines MCF-7 and/or MDA-MB-231 were eligible for the review. Totally, 31 articles were included in this review. Out of them, 23 studies investigated the effects of QT on MCF-7 cells and indicated that QT induces apoptosis in the cells. Of 15 studies that examined the effects of QT on MDA-MB-231 cells, 14 reports showed successful apoptosis. It is concluded that QT might be beneficial in the eliminating of breast cancer cells. However, further clinical trials are warranted to further verify these outcomes.
Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Female; Humans; MCF-7 Cells; Quercetin
PubMed: 33682528
DOI: 10.1080/01635581.2021.1897631